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Cardiovascular disease (CVD) is a major cause of death globally. Addressing cardiovascular risk factors, particularly dyslipidemia, represents the most robust clinical strategy towards reducing the CVD burden. Statins inhibit 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and represent the main therapeutic approach for lowering cholesterol and reducing plaque formation/rupture. The protective effects of statins extend beyond lowering cholesterol. MicroRNAs (miRNAs or miRs), small noncoding regulatory RNAs, likely mediate the positive pleiotropic effects of statins via modulation of lipid metabolism, enhancement of endothelial function, inhibition of inflammation, improvement of plaque stability, and immune regulation. miRNAs are implicated in statin-related interindividual variations in therapeutic response, directly via HMG-CoA reductase, or indirectly through targeting cytochrome P450 3A (CYP3A) functionality and proprotein convertase subtilisin/kexin type9 (PCSK9) biology.
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http://dx.doi.org/10.1016/j.tips.2018.09.005 | DOI Listing |
Eur Heart J
September 2025
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
Cardiovascular disease remains a major global health challenge, with dyslipidaemia being a key modifiable risk factor. While low density lipoprotein cholesterol (LDL-C) is the primary target for lipid-lowering therapies, recent evidence highlights the importance of triglycerides, apolipoprotein B (apoB), and lipoprotein(a) [Lp(a)] for residual cardiovascular risk. Current lipid-lowering therapies target key enzymes and proteins involved in cholesterol and lipid metabolism.
View Article and Find Full Text PDFFront Microbiol
August 2025
Biophysics Research Laboratory, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
Introduction: Red yeast rice (RYR) is produced through solid-state fermentation by Monascus genus. Its functional component, Monacolin K (MK), has the same structure as lovastatin and can effectively inhibit HMG-CoA reductase, thereby reducing serum cholesterol.
Methods: A combinatorial mutagenesis strategy integrating atmospheric room-temperature plasma and heavy-ion radiation was employed to generate mutant strains.
Chem Biodivers
September 2025
Department of Life Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.
The inhibition of 3-hydroxy-3-methylglutaryl coenzyme-A (HMGCR) activity carries considerable therapeutic significance, prompting the investigation of novel inhibitors to tackle associated health conditions and improve patient care. Seeking non statin scaffolds, we provide the first integrated evaluation of six terpenoids isolated from the brown alga Padina pavonia, expanding the species' chemical repertoire and establishing their activity against HMGCR. We have previously shown the anti-hyperlipidemia activity of P.
View Article and Find Full Text PDFPLoS One
September 2025
Faculty of Pharmacy, The University of Lahore, Lahore, Punjab, Pakistan.
Plant-derived compounds have recently gained attention owing to their better safety profile and multi-targeted actions. Charantin, a plant-based natural compound known for its diverse pharmacological properties, was investigated for its anti-hyperlipdemic activity using both in-silico and in-vivo approaches. A detailed network pharmacology analysis was used to predict charantin-related targets, cross-referenced with hyperlipidemia-associated genes from GeneCards, DisGeNET, and CTD.
View Article and Find Full Text PDFSci Rep
August 2025
School of Pharmacy and Medical Technology, Putian University, Putian, 351100, China.
The total synthesis of compound 1, a chiral diglyceride metabolite present in both humans and fungi, was achieved via a seven-step route, affording the target molecule in 2.33% overall yield. The synthetic strategy involved: (1) selective protection of the terminal hydroxyl group of chiral ketal 2 with a sterically hindered benzyl group, followed by ketal deprotection to yield benzyl ether 4; (2) protection of the terminal hydroxyl group of benzyl ether 4 with a bulky silyl protecting group, and subsequent esterification of the remaining hydroxyl with erucic acid to generate ester 6; (3) removal of the silyl protecting group from ester 6, followed by esterification of the liberated hydroxyl group with pentadecanoic acid to afford ester 8; and (4) selective deprotection of the benzyl group of ester 8 to furnish compound 1.
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